Assessment of BBB Disruption during RT using DCE MRI

描述（由申请人提供）：虽然放疗对高级别脑转移患者的中位生存有一定影响，但这些患者通常仍在局部进展，表明需要改进手段控制。化疗与放疗联合使用并没有显示出显著的改善，化疗有限的额外益处可能部分是由于抑制血脑屏障（BBB）运输的大分子大小。然而，辐射毒性研究结果显示，辐射可使内皮紧密连接松动，从而增加大分子向辐照组织的运输。由于对肿瘤区域的剂量明显高于对大多数正常大脑的剂量，这一效应实际上增加了所给药物摄取的特异性。这可能为提高化疗药物或放射增敏剂在放疗期间对肿瘤细胞的递送效率提供了机会。这种辐射效应需要更好地了解，以确定潜在的优势，至于日期，时间剂量和体积的依赖关系，以及修复的时间过程尚不清楚。这项研究是为了响应NCI/NIH/DHHS （PA-04-045）的体内癌症成像探索/发展拨款（in - Vivo Cancer Imaging Exploratory/Developmental grants）的申请，提出系统地表征正常大脑和肿瘤对一种分子大小与许多化疗药物相似的MRI造影剂的血管通透性的依赖性。患者对高级别胶质瘤或脑转移瘤进行放射治疗后，将进行一系列动态c增强（DCE） MRI扫描。这些扫描数据将被分析以量化血管通透性，这与剂量、体积、时间以及肿瘤与正常脑组织的存在有关。

DESCRIPTION (provided by applicant): While radiotherapy has made some impact on increased median survival for patients with high-grade glic brain metastases, these patients still generally progress locally, indicating the need for improved means control. The use of chemotherapy in combination with radiation has not shown significant improvement it is possible that the limited added benefit of chemotherapy is in part due to the large molecular size of inhibiting transport across the blood-brain barrier (BBB). Findings from radiation toxicity studies, however, reveal that radiation may loosen endothelial tight junctions, thus increasing transport of large molecules to irradiate tissue. As the dose to the tumor region is markedly higher than that delivered to most normal brain, this effect fact increase specificity of uptake of administered agents. This may provide a window of opportunity to improve efficiency of delivery of chemotherapeutic agents or radiosensitizers to tumor cells during radiotherapy. The of this radiation effect needs to be better understood to determine potential advantage, as to date, the time dose and volume dependence, and time course of repair are not well understood. This study, in response to a for applications on In Vivo Cancer Imaging Exploratory/Developmental grants from NCI/NIH/DHHS (PA-04-045 proposes to systematically characterize these dependencies on vascular permeability of normal brain and tumor to a MRI contrast agent that has a molecule size similar to many chemotherapeutic agents. Patient's und radiotherapy for high-grade gliomas or brain metastases will be followed by a sequence of dynamic c enhanced (DCE) MRI scans. Data from these scans will be analyzed to quantify vascular permeability, which related to dose, volume, time, and presence in tumor versus normal brain tissue.